To investigate circulating cytokine responsiveness in major burns in association with the systemic stress response system, we tested hypothalamic-pituitary-adrenal (HPA) axis markers in extensive burn cases treated in the Department of Plastic and Reconstructive Surgery at Nagasaki University. The HPA axis is a major stress response system, and the leukemia inhibitory factor (LIF) may be a potent mediator of the HPA axis; therefore, circulating LIF levels in burn patients were studied. Twenty extensively burned patients (burn surface area, >20%), ie, 10 women and 10 men, 37 to 77 years of age (average: 59.1 +/- 12.10 years), were assessed. Circulating LIF, adrenocorticotropic hormone (ACTH), other inflammatory markers, and 24-hour urinary free cortisol excretion levels were investigated. LIF levels were greater in patients who died than in those who survived (186.1 +/- 80.41, 83.5 +/- 64.49 pg/ml, respectively, P < .001) at 36 hours after injury. ACTH levels were more significantly elevated in fatal cases than in those who survived. (41.3 +/- 8.28, 25.2 +/- 7.84 pg/ml, respectively, P < .0001). Twenty-four hour (24 to 48 hours after injury) pooled urinary free cortisol excretion levels also were significantly greater in fatal cases than in the surviving patient group (235.0 +/- 36.49 microg/day, 69.0 +/- 18.04 microg/day, respectively, P < .0001). The correlation between serum LIF and urine free cortisol was significant (r = .30; P < .01) as was the correlation of serum LIF with plasma ACTH (r = .24; P < .01). Serum LIF as well as HPA axis activity markers is a good marker of disease severity and prognosis in patients with extensive burns.